ABSTRACT
The targeted screening and sequencing approaches for COVID-19 surveillance need to be adjusted to fit the evolving surveillance objectives which necessarily change over time. We present the development of variant screening assays that can be applied to new targets in a timely manner and enable multiplexing of targets for efficient implementation in the laboratory. By targeting the HV69/70 deletion for Alpha, K417N for Beta, K417T for Gamma, and HV69/70 deletion plus K417N for sub-variants BA.1, BA.3, BA.4, and BA.5 of Omicron, we achieved simultaneous detection and differentiation of Alpha, Beta, Gamma, and Omicron in a single assay. Targeting both T478K and P681R mutations enabled specific detection of the Delta variant. The multiplex assays used in combination, targeting K417N and T478K, specifically detected the Omicron sub-variant BA.2. The limits of detection for the five variants of concern were 4-16 copies of the viral RNA per reaction. Both assays achieved 100% clinical sensitivity and 100% specificity. Analyses of 377 clinical samples and 24 wastewater samples revealed the Delta variant in 100 clinical samples (nasopharyngeal and throat swab) collected in November 2021. Omicron BA.1 was detected in 79 nasopharyngeal swab samples collected in January 2022. Alpha, Beta, and Gamma variants were detected in 24 wastewater samples collected in May-June 2021 from two major cities of Alberta (Canada), and the results were consistent with the clinical cases of multiple variants reported in the community. © 2023 The Authors. Published by American Chemical Society.
ABSTRACT
Background: Novel Coronavirus pneumonia 2019 (COVID-19) is a systemic infectious disease with prominent involvement of the respiratory tract, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[1]. Systemic lupus erythematosus is charcterized by an aberrant immune response with the presence of circulating autoantibodies, lymphopenia, and proinfammatory[2]. They are immune-compromised and vulnerable to infections with immune-suppressants treatment. However, data regarding the impact of COVID-19 pandemic in patients with SLE and drug use were relatively scarce. Objectives: The prevalence of COVID-19 in SLE patients was estimated by means of meta-analysis, and the effect of the use of anti-rheumatic drugs on the clinical outcome of SLE patients with COVID-19 was investigated. Methods: Cross-sectional investigations and case series on SLE and COVID-19 published by CBM, CNKI, China Science and Technology Journal Database, Wan Fang Data, PubMed, Embase, Web of Science, Cochrane Library and Medline from its establishment to November 10, 2021 were searched. Random effects model was used to pool data. Heterogeneity and risk of bias was examined with I-squared index (I2) statistic. Inconsistency was evaluated by using the I2. Egger tests were used for the evaluation of potential publication bias (STATA v.12.0). Results: A total of 14 studies comprising 5365 patients were identifed (Table 1). Overall prevalence of COVID-19 in SLE patients was 1.5% (95%CI: 1.2%-1.8%). Eight of the studies included patients who used hydroxychloroquine as part of their treatment regimen, with 29.8% (95%CI: 25.8%-33.8%) hospitalization rates and 14.6% (95%CI: 11.5%-17.8%) adverse outcome rates. Among patients treated with hydroxychloroquine throughout the course of disease, the prevalence was 0.7% (95%CI: 0.4%-1.0%, Figure 1). Conclusion: Patients with SLE had a higher risk of COVID-19. Hydroxychloro-quine might beneft to reduce the overall hospitalization rate and prevalence rate of COVID-19, and alleviate infammatory damage in the chronic stage of viral infection by inhibiting over activation of the immune system.
ABSTRACT
Background: To evaluate the efficacy and safety of different treatment modalities of regorafenib in patients with previously treated metastatic colorectal cancer (mCRC) in the real-world setting. Methods: Individual patient data were retrieved from three leading oncology centers in China from January 2016 to March 2021. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS) and safety. Results: The characteristics of patients who received treatment are shown in the table. Twenty-one patients received regorafenib combined with capecitabine as the second-line treatment for those who cannot visit hospital for their chemotherapies because of the COVID-19 pandemic. The median PFS and median OS were 8 (95% CI 4.36 -11.00) months and 26.9 (95%CI 20.54 -NR) months. 101 patients received regorafenib and 69 patients received regorafenib plus immune checkpoint inhibitor (ICIs) as third or higher line treatment, the overall response was 4.1%(7/170), including one complete response. Patients combined with ICIs have longer PFS than those with regorafenib monotherapy (median PFS = 3.3 versus 2.1 months;p = 0.01). Starting dose was 80, 120 and 160 mg in 64, 40 and 39 patients, respectively. Dose reduction was observed in 43.3% (39/79) of patients receiving 120 and 160 mg as the initial dose. Conclusions: Different treatment modalities of regorafenib all showed promising efficacy and safety in the treatment of mCRC. Regorafenib combination is better than regorafenib monotherapy. Regorafenib combined with capecitabine provided a new treatment strategy during the epidemic but requires further investigation.
ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse model. Cryo-electron microscopy characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a previously uncharacterized conformational epitope, which was only accessible when the RBD was in an open conformation. Biochemical, cellular, virological, and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncovered broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.